Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693628 | SCV000821503 | likely pathogenic | Familial hemiplegic migraine | 2019-06-27 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual affected with ATP1A2-related disorder (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 812 of the ATP1A2 protein (p.Asp812His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |